基于出生队列研究生命早期体格发育动态与青少年血压的复杂关联

青少年血压偏高可影响成人心血管疾病的发生发展；不良体格发育的早期干预有望能促进青少年血压健康，为降低成人心血管疾病负担提供新的思路，从而实现心血管病的预防关口前移，但目前仍缺乏婴幼儿期的队列研究证据支持。本项目基于一项自孕期开始随访长达14年的出生队列，拟研究：（1）联合应用基于组轨迹模型、分式多项式混合效应、相对增长量等轨迹分析前沿技术，全面地刻画人群及个体从出生到青少年身长/身高、BMI等体格指标的发育变化，特别是0-2岁及2岁后发育的延续性；（2）明确上述不同年龄体格发育动态与青少年血压的关联强度，及其与孕期、出生结局、性发育时相等关键变量的作用网络；（3）借助于孟德尔随机化设计，验证上述关联的因果效应。本项目的完成，可阐明0-2岁及2岁后体格发育变化对青少年血压效应强度的差异，明确早期干预的敏感窗口期和目标人群，多角度、多层次地为促进人群全生命周期心血管健康提供科学依据。

The blood pressure of adolescents affects the occurrence and development of the cardiovascular disease. Early-life intervention for poor physical growth is expected to improve adolescent blood pressure health and provides new thoughts for reducing the burden of cardiovascular disease during adulthood, consequently achieving the advancement of cardiovascular disease prevention. However, this hypothesis still needs scientific evidence based on cohort studies among the infant and young child population. This project takes advantage of a birth cohort that has been followed for 14 years since pregnancy and proposes the following aims. 1) Jointly apply cutting-edge techniques of trajectory analysis such as group-based trajectory modeling, mixed effect models with fractional polynomial functions, and relative growth measures to comprehensively describe the dynamic changes of physical growth (i.e., length/height and BMI) from birth to adolescence within the population and individuals, and especially the continuity of growth between 0-2 and after 2 years old. 2) Clarify the associations between dynamic changes of physical growth at different ages and adolescent blood pressure, and its net-relationships with pregnancy exposures, birth outcomes, and puberty. 3) Confirm the causal associations using the Mendelian randomization design. The promising results would quantify the strength of causal associations of dynamic growth during 0-2 and after 2 years old with adolescent blood pressure, identify the critical window and key population, and finally promote the cardiovascular health of the population from multiple lenses and a life-course perspective.